ROLE OF PLATELET-ACTIVATING-FACTOR IN GENTAMICIN AND CISPLATIN NEPHROTOXICITY

The present study was undertaken to evaluate the effects of platelet activating factor (PAF) antagonists on nephrotoxicity induced by gentamicin (GENTA) and cisplatin (DDP) in rats. PAF infusion provoked a 56% decline in single nephron (SN) GFR due to a decrease in glomerular plasma flow (Q(A), 55%), glomerular transcapillary hydraulic pressure (DELTA-P, 13%), and glomerular ultrafiltration coefficient (K(f), 37%). Four days after a single dose of DDP (6 mg/kg, i.p.) we observed non-oliguric acute renal failure (ARF) with reduced SNGFR (45%), Q(A) (46%) and DELTA-P (10%) and unchanged K(f). GENTA administration for 10 days (40 mg/kg, i.p. daily) induced a decline in SNGFR (40%), Q(A) (41%) and K(f) (41%). Chronic treatment with a GENTA + PAF antagonist (BN 52021) partially prevented the decline in SNGFR (22%) by an amelioration in Q(A) (25%) and K(f) (13%). However, simultaneous treatment with DDP and BN 52063 completely prevented the ARF induced by DDP, normalizing all parameters of renal function. Thus, PAF may be a potential mediator involved in the nephrotoxicity induced by GENTA and DDP.